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To describe the frequency of opioid-induced neurotoxicity (OINT) after opioid conversion (OC) to methadone using the Stop-and-Go (SAG) method in cancer patients with inadequate pain control, and to identify factors associated with OINT. This multicenter retrospective cohort study included adult hospitalized cancer patients who underwent OC to methadone using the SAG method for poor pain control at two comprehensive cancer centers between January 2018 and October 2022. Patients were monitored 14days after OC, and variables related to OINT were analyzed. Ethical approval was obtained. A total of 372 patients underwent OC using the SAG method. The mean morphine-equivalent daily dose (MEDD) before OC was 212.2mg (SD 128). OINT occurred in 70 patients (18.8%). Methadone was permanently discontinued in 2 patients (2.8%) and temporarily withheld in 7, while 61 were managed with hydration and a 15-20% methadone dose reduction. No patient required naloxone. OINT was less frequent in younger patients (mean age 59.4 vs. 63years; p = 0.032) and showed a trend toward lower incidence in women (13% vs.22%; p = 0.065). Preexisting cognitive impairment or delirium was associated with OINT (52.4% vs.16.8%; p < 0.001). The mean time from OC to death was shorter among patients with OINT (2.1months; SD 3.9) compared with those without OINT (3.6months; SD 6.4; p = 0.012). OC to methadone using the SAG method in patients with low-to-moderate MEDD was associated with a relatively low OINT frequency (18.8%). These findings suggest that SAG method in patients with low-to-moderate MEDD before OC may be safe, particularly for younger patients and those without cognitive impairment.

Nasopharyngeal carcinoma is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy is the cornerstone of locoregional treatment of non-disseminated disease and, in combination with chemotherapy, improves survival rates. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy, and patients may achieve a long survival time. In these guidelines (updated in 2025), we summarize current evidence and available therapies for the medical management of advanced nasopharyngeal carcinoma.

Background: Natriruetic peptide (NP) screening is recommended for HF prevention in diabetes mellitus (DM), with NT-proBNP &gt;125 pg/mL considered abnormal. However, evidence supporting this threshold is derived primarily from shorter-term studies. Lifetime risk (LTR) estimates for HF across NT-proBNP concentrations in DM is unknown. Methods: Participant-level data from 6 prospective cohorts (ARIC, MESA, CHS, FOS, FHS Generation 3, CRIC) and the Look AHEAD trial control group were pooled excluding participants with prevalent HF or ASCVD at baseline. Participants were stratified according to well-established NP thresholds ( Figure) . LTR of HF was determined at different index ages using the pratical incidence estimator macro with modified Kaplan-Meier methods that uses age as a time scale and mortality as a competing risk. A positive control group of adults with DM and prevalent CVD was analyzed separately. Results: Among 5,986 participants (age 61 y, 45% male, 25% Black), 1,134 developed HF over 79,347 person-years (14.3 per 1,000 person-years). At index age 55 y, the LTR of HF through 90 years was 34.4%. Lifetime risk of HF increased progressively across increasing NT-proBNP categories at each index age ( Figure 1A and 1B ). At index age 55 y, the LTR estimate for the NT-proBNP &gt;125 pg/mL category (48.7%) was comparable to the positive control group with prevalent CVD (n = 1,687; 51.7%). LTR of HF was higher in Black (vs. non-Black) adults at every category with detectable NT-proBNP and was comparable to prevalent CVD at lower thresholds (50-125 pg/ml) ( Figure 1B ). LTR of HF among adults with low short-term HF risk (based on WATCH-DM or 10-y HF PREVENT risk scores) and NT-proBNP &gt;125 pg/mL was high and comparable with the prevalent CVD group. Adding NT-proBNP to 30-year PREVENT HF risk score substantially improved LTR prediction performance (AUROC for 30-year risk: 0.569 to 0.685, p&lt;0.001). Conclusions: In adults with DM, higher NT-proBNP concentrations identify higher LTR of HF, with the highest risk noted among those with concentrations &gt;125 pg/ml supporting the current guideline recommended screening thresholds to discriminate lifetime risk. Lifetime risk of HF associated with NT-proBNP concentrations vary by race with disporporationtely high risk observed among Black adults.

BackgroundThe health-related quality of life (HRQoL) of patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) is impacted by both disease- and treatment-related factors. Treatments that preserve and maximize HRQoL in this setting represent a substantial unmet need.MethodsKEYNOTE-412 (NCT03040999) was a randomized, double-blind, placebo-controlled phase 3 study of pembrolizumab plus chemoradiotherapy (CRT) versus placebo plus CRT for maintenance therapy in participants with treatment-naïve LA HNSCC. Patient-reported outcomes (PROs) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ Head and Neck 35 (H&N35) were pre-specified secondary endpoints and administered at baseline and throughout the study. Least squares mean (LSM) change from baseline was assessed using a constrained longitudinal data analysis model. No formal statistical significance testing was performed.ResultsThe PRO analysis population included 395 participants randomized to receive pembrolizumab plus CRT and 397 to receive placebo plus CRT. Completion rates for all assessed PROs were >95% at baseline and >66% at week 45. LSM change from baseline to week 45 was similar between groups across EORTC QLQ-C30 and QLQ-H&N35 subscale scores. There were no notable differences in empirical mean change or the proportion of participants with improvement, stability, or deterioration from baseline to week 45 between treatment groups.ConclusionThe addition of pembrolizumab to CRT did not meaningfully impact HRQoL in participants with LA HNSCC.

Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P= 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

A field trial was carried out in Parbhani to validate the technology for managing soil-borne and seed-borne safflower diseases. The purpose of the trial wasto compare farmer practices with the strain (Th4d) used as a seed dresser. Before seed was sown, it was treated with the fungicides Carbendazim 12 % +Mancozeb 63 % @ 0.2 % and . In comparison to farmers’ Trichoderma harzianum practices, where the disease incidence was 11.3 %, the seed treatments harzianum Trichoderma harzianum Trichoderma Th4d SC @ 2ml/kg and Th4d WP @ 10g/kg were found to be the most effective, with much lower incidence of seed/soil transmitted disease at 5.3%.The highest seed yields (1034 kg/ha and 1055 kg/ha) were likewise reported by the treatments Th4d SC @2ml/kg and Trichoderma harzianum